Diagnostic tape unit and diagnostic measuring system

ABSTRACT

The invention concerns a diagnostic tape unit with a test tape that can be wound onto a spool which comprises a transport tape and a plurality of test elements mounted thereon, where the test elements have an analytical reagent layer, a carrier foil supporting the reagent layer and a piece of adhesive tape connecting the carrier foil with the transport tape, and where the front side of the reagent layer facing away from the carrier foil is designed for the application of a sample substance. According to the invention it is proposed that the test elements in combination with the light transmitting transport tape in each case form an optical multi-layer system for a rear-side reflection-photometric measurement of the reagent layer.

CLAIM OF PRIORITY

The present application is a divisional of U.S. patent application Ser.No. 12/940,368 filed on Nov. 5, 2010, which is a continuationapplication based on and claiming priority to international applicationPCT/EP2009/055450, filed May 6, 2009, which claims the priority benefitof European Application 08155742.3, filed May 6, 2008, each of which arehereby incorporated by reference in their respective entireties.

TECHNICAL FIELD OF THE INVENTION

The invention concerns a diagnostic tape unit, in particular a tapecassette for blood sugar tests with a test tape that is wound onto orcan be wound onto a spool as a tape reel, the test tape comprising atransport tape and a plurality of test elements which are mountedthereon. The invention additionally concerns a measuring system for theuse of such a tape unit.

BACKGROUND

Tape units have been designed for blood sugar tests in order to furtherimprove the user-friendliness compared to test strip systems availableon the market. Thus, in order to simplify the handling, a large numberof test elements can be compactly stored on a rollable transport tapeand also be disposed of again after use by means of the tape transport.Such a tape unit can be advantageously inserted into a hand-held deviceas a consumable in the form of a cassette in order to allow the user tocarry out substantially automated self tests.

With conventional dry chemistry test strips, reagent fields are mountedon a relatively thick reagent carrier. An optical reflection measurementcan be carried out relatively easily with such a one-layer system.However, a test tape with a plurality of tests that is spooled in theform of a tape reel cannot be realized with this.

On this basis the object of the invention is to further develop the tapeconcepts known in the prior art and to specify a tape unit designed fora reliable measurement even as a mass-produced article of the typestated above as well as a measuring system therefor.

SUMMARY

This object and others that will be appreciated by a person of ordinaryskill in the art have been achieved according to the embodiments of thepresent invention disclosed herein. In one embodiment, the presentinvention comprises a diagnostic tape unit, in particular a tapecassette for blood sugar tests with a test tape that is wound onto orcan be wound onto a spool as a tape reel, the test tape comprising atransport tape and a plurality of test elements which are mountedthereon, where the test elements include an analytical reagent layer, acarrier foil supporting the reagent layer and a piece of adhesive tapeconnecting the carrier foil with the transport tape, and where the frontside of the reagent layer facing away from the carrier foil is designedfor the application of a sample substance.

The combination of features stated in the independent patent claims isproposed to achieve this object. Advantageous embodiments and furtherdevelopments of the invention are derived from the dependent claims.

The embodiments of the present invention are based on the idea ofenabling a sample application on the front-side and measurement on therear side with a test tape having spaced apart test fields. Accordinglyit is proposed according to the embodiments that the test elements incombination with the light transmitting transport tape in each case forman optical multi-layer system for a rear-side, reflection-photometricmeasurement of the reagent layer. The multi-layer assembly enablesrelatively thin prefabricated test carriers to be integrated into a tapereel and the uniform optical multi-layer composite enables thereflectance to be detected by a measuring apparatus at an exposedsection of the test tape independently of the handling side.

In order to obtain a measuring signal which has the required quality fordiagnostic applications, when the refractive index and/or thetransmission and/or the haze of the layers of the multi-layer system isformed by the carrier foil, the piece of adhesive tape and the transporttape are matched on each other within predetermined tolerances. In thisconnection it is particularly advantageous when the refractive index ofthe transport tape, the carrier tape and the piece of adhesive tape isin each case between about 1.4 and 1.7, for example between about 1.5and 1.6.

Interfering effects can be further reduced by means of the fact that theindividual layers of the multi-layer system have a maximum refractiveindex difference of about 0.2, for example less than about 0.1.

In one embodiment, the total refractive index is about 1.5, and thedeviation in the refractive index is less than 0.1.

Further improvements can be achieved when the transport tape, the pieceof adhesive tape and the carrier foil each have a transmission in thevisible wavelength range of more than about 80%, for example betweenabout 85% and 92%, and when the total transmission of the multi-layersystem in the visible wavelength range is at least about 80%.

For a reproducible measurement, in certain embodiments the transmissiontolerance is less than 5% for the entirety of the test elements of atest tape.

In order to adequately reduce scattering losses it is advantageous whenthe optical haze of the carrier tape and of the piece of adhesive tapein the visible wavelength range is less than 10%, for example about 8%.It is also favorable when the optical haze of the transport tape in thevisible wavelength range is less than 3%, for example about 2.5%, andwhen the total optical haze of the multi-layer system in the visiblewavelength range is less than 20%, for example about 15%.

In order to be able to take into consideration interfering effects dueto the manufacturing process, a decrease in the haze of the multi-layersystem should take place in a given time interval in particular of about1 to 2 weeks after its manufacture, where subsequently the haze shouldremain relatively constant.

In order to adequately limit variants within a given tape unit, the hazetolerance for the entirety of the multi-layer systems of a test tapeshould be less than about 5%.

In other embodiments, a multi-layer piece of adhesive tape is used whichcomprises a transparent foil substrate furnished on both sides with anadhesive layer.

In yet other embodiments, the transport tape and the carrier foilcomprise a PET film. In general polymer foils can be used. In additionto polyethylene terephthalate (PET), other examples of materials for thetransport tape and carrier foil are polyvinyl fluoride (PVF),polyethylene (PE), polypropylene (PP), polyvinylidene difluoride (PVDF),polyvinyl chloride (PVC), polystyrene (PS), ethylene/tetrafluoroethylenecopolymers (ETFE), polycarbonate and propylene carbonate.

In yet other embodiments, the thickness of the carrier foil is betweenabout 20 and 25 μm, the thickness of the transport tape is between about10 and 15 μm and the thickness of the piece of adhesive tape is betweenabout 30 and 50 μm.

In order to take into account interfering effects which result from aspecific configuration, in embodiments in which an analyte contained inthe sample substance in particular in the form of a body fluid, inparticular blood, is determined by a relative reflectance measurement,calibration data are typically assigned to the test elements whichdefine the concentration of the analyte as a function of the measuredreflectance.

Another aspect of the invention concerns a diagnostic measuring systemin particular for blood sugar tests with a diagnostic tape unitaccording to the invention and a reflection photometric arrangementoriented towards the rear side of the reagent layer of the test elementlocated in a measuring position which comprises a light source and aphotodetector where the detector is arranged outside the directreflection path of the measuring light radiated by the light sourcethrough the multi-layer system onto the reagent layer.

In this connection in certain embodiments the light source generates alight spot of less than about 1 mm² on the rear side of the reagentlayer where a granularity of the reagent layer serves as a diffuser.

The invention is to be explained in more detail by the following figuresand examples.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of the embodiments of the presentinvention can be best understood when read in conjunction with thefollowing drawings, where like structure is indicated with likereference numerals and in which:

FIG. 1 shows a diagnostics tape unit in the form of a tape cassette in asectional perspective view.

FIG. 2 shows the test tape of the tape cassette in a longitudinalsection of a part thereof in the area of a test element.

FIG. 3 shows a reflectometric measuring arrangement oriented towards thetest tape in a diagrammatic view.

In order that the present invention may be more readily understood,reference is made to the following detailed descriptions and examples,which are intended to illustrate the present invention, but not limitthe scope thereof.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE PRESENT INVENTION

The following descriptions of the embodiments are merely exemplary innature and are in no way intended to limit the present invention or itsapplication or uses.

The tape cassette 10 shown in FIG. 1 can be used as a consumable in ahand-held device (not shown) to carry out a plurality of blood sugarself-tests. The cassette comprises a test tape 12, a supply spool 14 tounwind unused test tape and a take-up spool 16 to wind used test tape,where the test tape 12 has a rollable transport tape 18 and a pluralityof spaced-apart test elements 20 mounted thereon.

The unused test tape is stored protected from environmental influencesin the form of a tape reel on the supply spool 14. The test tape 12 canbe wound on by means of a rotary drive which engages with the take-upspool 16 such that the test elements 20 can be successively madeavailable for the user at an application site 22. At this site a drop ofblood can be applied in a simple manner on the exposed front side 24 ofthe respective active test element 20, while a rear-sidereflection-photometric measurement is carried out by a measuringarrangement in the instrument that engages in the measuring chamber 26of the cassette 10. The used section of test tape is disposed of on thetake-up spool 16. In this manner it is possible to process approximately50 tests without requiring instrument intervention or laboriousoperating steps by the user.

As shown in FIG. 2, the transport tape 18 together with the attachedtest elements 20 forms a multi-layer composite structure or amulti-layer system which is based on a simple manufacturing process asdescribed in EP-A 1 593 434, the disclosure of which is herebyincorporated by reference herein in its entirety. The test elements 20are glued onto the transport tape 18 as test labels by means of a pieceof double-sided adhesive tape 28. For this purpose the piece of adhesivetape 28 comprises a liner foil 30 which is furnished on both sides withan adhesive layer 32, 32′. The detection reaction takes place in a thinreagent layer 34 which is applied to a carrier foil 36 as a drysubstance and which is held there by means of a piece of adhesive tape28. The magnitude of a color change of the reagent is in this connectionfunctionally related to the concentration of the analyte to be measured(in this case blood glucose). The applied body fluid can be spreadtwo-dimensionally on the application side of the reagent layer 34 bymeans of a net-like spreading layer 38.

The glucose concentration is determined by reflectance photometry inwhich a relative reflectance value is determined as a quotient of theend value and the start value of the test element 20 in order to takeinto account constant interfering factors. For this the initialreflectance value of the test element is measured before sampleapplication and the reflectance is measured again after a time intervalafter adding the sample to the reagent layer. The first measurement aswell as the subsequent measurements include interfering factors whichirrespective of the wanted signal make contributions to the measuredsignal. The sample concentration is then calculated by means of acalculation rule (function curve) stored in the instrument. Thisfunction curve can be determined by calibrating the measuring system.Hence, this allows constant interfering factors to be taken intoconsideration for the system calibration.

However, for a reliable reflectance measurement the optical interferingeffects must be small compared to the measured signal. In the case ofconventional test strips, measurements are made only through a one-layerreagent carrier, whereas different foils and adhesive layers must betaken into account in the multi-layer composite structure according toFIG. 1. In this connection it should be noted that all foils availableon the market have tolerances with regard to their opticalspecifications which are due to the manufacturing processes. Thus, theoptical light path is affected by the transparency, absorption,refractive index and scattering parameters of each individual componentand by the interaction of the components that are used.

Hence, in order to be able to carry out a reflectance measurement withthe accuracy required for blood sugar measurements, it is not possibleto use just any foils, but rather in the multi-layer tape configurationdescribed above special precautionary measures and matching with regardto the optical properties are necessary as summarized in the followingin table 1.

The magnitude of the wanted signal decreases with increasingtransparency or transmission of the foils. In addition the signalquality is also affected by the surface scattering and volumescattering. Both together can be detected by a measurement of opacity.The said parameters can be determined by a standard measurementprocedure according to the ASTM-D 1003-61 method A standard (standardtest method for haze and luminous transmittance of transparentplastics). In this procedure the scattering in the forwards direction ofthe transmitted light is detected by means of a so-called haze metersuch as that which is for example sold under the trade name “BYK GardnerHaze-Gard Plus”. The mode of operation of this instrument is based onirradiating a collimated bundle of light centrally through a foil sampleinto the entrance of an Ulbricht sphere in which a light trap isdisposed at a sphere exit that is diametrically opposite to the sphereentrance and the scattered light is detected at an angle of 90°centrally in relation to the axis of the through beam. This allows adifferentiation to be made between unscattered light and light scatteredby the haze of the foil in the forwards direction. An area of the sphereis covered by a scattering standard for the transmission measurement.

Surprisingly it turned out that such haze measurements in the forwardsdirection also enable an influencing variable to also be obtained forreflectance measurements in the backwards direction where theinfluencing variable can be measured using standardized instruments. Itwas found that for a multi-layer structure there was a linearrelationship between the reflectance blank value detected in thediagnostic measuring system and the material parameter detected in thehaze meter (haze H) as a function of the layer thickness. In this mannerit is possible to translate a variation in the scattering which is stillacceptable for the actual measurement signal into a defined tolerancerange of the haze signal and thus ensure a quality control for the foilsthat are used. In this connection it must be born in mind that as thehaze increases the ranges for variation and tolerance must also berestricted.

In one embodiment, the long flexible transport tape 18 comprises PET andhas a thickness d of about 12 μm and a refractive index n of about 1.6.In such an embodiment, the transport tape 18 should be substantiallylight permeable or transparent and the spectral transmission T in thewavelength range between about 400 and 900 nm should be more than about85%. The haze (haze H) should be at about 2.5%. As stated above theadherence of tolerance ranges (tolerance widths) ensures measuringprecision within the allowed limits in a mass production. Thetransmission tolerance ΔT should be less than 2% for the transport tape18 cut to the required length, and the haze should vary by less than0.5%.

The other layers in the multi-layer system should be specially matchedaccording to table 1:

TABLE 1 d n T ΔT H ΔH transport tape 18 12 μm 1.6 >88% <2% 2.5% <0.5%  piece of adhesive tape 28 42 μm 1.5 >85% <3% 8.0% <3% PET carrier foil36 23 μm 1.6 >88% <2% 8.0% <1% total system 77 μm 1.5 >80% <5%  15% <5%18, 28, 36

The uniformly determined measured values for the total assemblycomprising transport tape 18, piece of adhesive tape 28 and carrier foil36 are stated in the last line of table 1. A particular problem wasobserved for the total system with regard to the stability of themeasured values in that there was a decrease in the haze values withinthe first one to two weeks after manufacture. Afterwards the measuredvalues remained essentially stable over time. The individual componentsdo not exhibit such a behavior before their assembly. An explanation isthat the initially increased haze is due to the inclusion of air bubbleswhen the individual components are assembled to form the total systemwhich results in an increased scattering. The decrease in the measuredhaze values over time is then caused by the escape of the enclosed airby diffusion.

FIG. 3 shows a diagnostic measuring system as implemented in a portableblood sugar measuring device with an inserted tape cassette 10. Themeasurement of the reagent layer 34 from the rear side is by means of areflection photometric arrangement 40 in the instrument which comprisesa light source (LED 42) and an optical detector (photodiode 44). Theirradiated light beam 46 is focused by an optical system (collectinglens 48) onto a small light spot on the rear side of the reagent layer44 where its granularity acts as scattering bodies. In this case thedetector 44 is outside the range of angles of reflection of the directlyreflected light fraction such that essentially only scattered light isdetected.

Hence, the system is designed such that the test field formed by thereagent layer 34 is illuminated at high intensity. The measuring lightthereby interacts with the reagent and is scattered as a function ofabsorption and transmission. The scattered useful light 50 impinges onthe detector 44 according to the solid angle of detection. However, atthe detector the interfering light 52 scattered or reflected by theother components 18, 28, 36 is also detected (the optical path issimplified symbolically in FIG. 3). The quality of the measurementsignal is therefore derived from the ratio of useful light tointerfering light. The described adaptation of the optical properties ofthe elements located in the optical path with regard to refractiveindex, transmission, absorption and scattering properties in the rangeof the illumination wavelength has the effect that the measurementsignal corresponds to the required quality.

The functional relationship between the measured reflectance and theconcentration of the analyte can be described by a calibration curve.The measuring instrument controlled by microelectronics can thus assignthe correct concentration value to any determined reflectance anddisplay this on a display. The calibration curve is determined using thesame reagents in the described test field arrangement. The scatteredlight fractions resulting from the specific structure can therefore betaken into consideration in the calibration. The process-relatedvariations of the different interfering factors occur within a certaintolerance. The allowed tolerance for these interfering factors isderived from the predetermined and allowed limits to the concentrationlevel of the relevant analyte.

The features disclosed in the above description, the claims and thedrawings may be important both individually and in any combination withone another for implementing the invention in its various embodiments.

It is noted that terms like “preferably”, “commonly”, and “typically”are not utilized herein to limit the scope of the claimed invention orto imply that certain features are critical, essential, or evenimportant to the structure or function of the claimed invention. Rather,these terms are merely intended to highlight alternative or additionalfeatures that may or may not be utilized in a particular embodiment ofthe present invention.

For the purposes of describing and defining the present invention it isnoted that the term “substantially” is utilized herein to represent theinherent degree of uncertainty that may be attributed to anyquantitative comparison, value, measurement, or other representation.The term “substantially” is also utilized herein to represent the degreeby which a quantitative representation may vary from a stated referencewithout resulting in a change in the basic function of the subjectmatter at issue.

Having described the present invention in detail and by reference tospecific embodiments thereof, it will be apparent that modification andvariations are possible without departing from the scope of the presentinvention defined in the appended claims. More specifically, althoughsome aspects of the present invention are identified herein as preferredor particularly advantageous, it is contemplated that the presentinvention is not necessarily limited to these preferred aspects of thepresent invention.

1-21. (canceled)
 22. A diagnostic measuring system comprising: adiagnostic tape unit comprising a tape cassette for blood sugar tests,the tape cassette having a test tape that is wound onto or can be woundonto a spool as a tape reel, the test tape comprising alight-transmitting transport tape and a plurality of spaced apart testelements mounted thereon, the test elements each comprising ananalytical reagent layer supported on a carrier foil layer, and furtherincluding an adhesive tape layer connecting the carrier foil layeradhered on one side with the transport tape adhered on an opposite side,wherein a front side of the reagent layer faces away from the carrierfoil layer and is configured for the application of a sample substance,the test elements in combination with the transport tape in each casefoaming an optical multi-layer system for a rear-sidereflection-photometric measurement of the reagent layer, wherein thetransport tape, the adhesive tape layer and the carrier foil layer ofeach test element each have optical properties comprising refractiveindex, transmission and haze, and wherein at least one optical propertyof the transport tape, adhesive tape layer and carrier foil layer arematched within predetermined tolerances; and a reflection photometricarrangement oriented towards the rear side of the reagent layer of thetest element located in a measuring position, the reflection photometricarrangement comprising a light source and a photodetector where thephotodetector is arranged outside the direct reflection path of themeasuring light radiated by the light source through the multi-layersystem onto the reagent layer.
 23. The diagnostic measuring systemaccording to claim 22, wherein the light source generates a light spotof less than about 1 mm² on the rear side of the reagent layer, whereina granularity of the reagent layer serves as a scattering body.
 24. Thediagnostic measuring system according to claim 22, wherein therefractive index of the transport tape, the carrier tape and theadhesive tape is in each case between about 1.4 and 1.7.
 25. Thediagnostic measuring system according to claim 24, wherein therefractive index of the transport tape, the carrier tape and theadhesive tape is in each case between about 1.5 and 1.6.
 26. Thediagnostic measuring system according to claim 22, wherein theindividual layers of the multi-layer system have a maximum refractiveindex difference of about 0.2.
 27. The diagnostic measuring systemaccording to claim 26, wherein the individual layers of the multi-layersystem have a refractive index difference of less than about 0.1. 28.The diagnostic measuring system according to claim 22, wherein the totalrefractive index of the multi-layer system is about 1.5.
 29. Thediagnostic measuring system according to claim 22, wherein the transporttape, the adhesive tape and the carrier foil layer each have atransmission in the visible wavelength range of more than 80%.
 30. Thediagnostic measuring system according to claim 29, wherein the transporttape, the adhesive tape and the carrier foil layer each have atransmission in the visible wavelength range of between about 85% and92%.
 31. The diagnostic measuring system according to claim 22, whereinthe total transmission of the multi-layer system in the visiblewavelength range is at least about 80%.
 32. The diagnostic measuringsystem according to claim 22, wherein the transmission tolerance is lessthan about 5% for the entirety of the test elements of a test tape. 33.The diagnostic measuring system according to claim 22, wherein theoptical haze of the carrier foil layer and of the piece of adhesive tapein the visible wavelength range is less than about 10%.
 34. Thediagnostic measuring system according to claim 33, wherein the opticalhaze of the carrier foil layer and of the adhesive tape in the visiblewavelength range is less than about 8%.
 35. The diagnostic measuringsystem according to claim 22, wherein the optical haze of the transporttape in the visible wavelength range is less than about 3%.
 36. Thediagnostic measuring system according to claim 35, wherein the opticalhaze of the transport tape in the visible wavelength range is less thanabout 2.5%.
 37. The diagnostic measuring system according to claim 22,wherein the total optical haze of the multi-layer system in the visiblewavelength range is less than about 20%.
 38. The diagnostic measuringsystem according to claim 37, wherein the total optical haze of themulti-layer system in the visible wavelength range is less than about15%.
 39. The diagnostic measuring system according to claim 22, whereinthe adhesive tape comprises a transparent foil substrate furnished onboth sides with an adhesive layer.
 40. The diagnostic measuring systemaccording to claim 22, wherein the transport tape and the carrier foileach comprise a PET film.
 41. The diagnostic measuring system accordingto claim 22, wherein an analyte contained in a sample substance in theform of a body fluid can be determined by a relative reflectancemeasurement, wherein calibration data are assigned to the test elementswhich define the concentration of the analyte as a function of themeasured reflectance.